Floresta Giuseppe, Abbate Vincenzo
Department of Analytical, Environmental and Forensic Sciences, Institute of Pharmaceutical Sciences, King's College London, London, UK.
Med Res Rev. 2022 Jul;42(4):1588-1606. doi: 10.1002/med.21885. Epub 2022 Mar 16.
Tyrosine-protein kinase Met-also known as c-Met or HGFR-is a membrane receptor protein with associated tyrosine kinase activity physiologically stimulated by its natural ligand, the hepatocyte growth factor (HGF), and is involved in different ways in cancer progression and tumourigenesis. Targeting c-Met with pharmaceuticals has been preclinically proved to have significant benefits for cancer treatment. Recently, evaluating the protein status during and before c-Met targeted therapy has been shown of relevant importance by different studies, demonstrating that there is a correlation between the status (e.g., aberrant activation and overexpression) of the HGFR with therapy response and clinical prognosis. Currently, clinical imaging based on positron emission tomography (PET) appears as one of the most promising tools for the in vivo real-time scanning of irregular alterations of the tyrosine-protein kinase Met and for the diagnosis of c-Met related cancers. In this study, we review the recent progress in the imaging of c-Met aberrant cancers with PET. Particular attention is directed on the development of PET probes with a range of different sizes (HGF, antibodies, anticalines, peptides, and small molecules), and radiolabeled with different radionuclides. The goal of this review is to report all the preclinical imaging studies based on PET imaging reported until now for in vivo diagnosis of c-Met in oncology to support the design of novel and more effective PET probes for in vivo evaluation of c-Met.
酪氨酸蛋白激酶Met，也称为c-Met或HGFR，是一种膜受体蛋白，具有相关的酪氨酸激酶活性，在生理上受其天然配体肝细胞生长因子（HGF）刺激，并以不同方式参与癌症进展和肿瘤发生。临床前研究已证明，用药物靶向c-Met对癌症治疗具有显著益处。最近，不同研究表明，在c-Met靶向治疗期间及之前评估蛋白状态具有重要意义，这表明HGFR的状态（如异常激活和过表达）与治疗反应和临床预后之间存在相关性。目前，基于正电子发射断层扫描（PET）的临床成像似乎是对酪氨酸蛋白激酶Met的不规则改变进行体内实时扫描以及诊断与c-Met相关癌症的最有前景的工具之一。在本研究中，我们综述了PET对c-Met异常癌症成像的最新进展。特别关注了一系列不同大小（HGF、抗体、抗独特型抗体、肽和小分子）且用不同放射性核素标记的PET探针的开发。本综述的目的是报告迄今为止基于PET成像的所有临床前成像研究，用于肿瘤学中c-Met的体内诊断，以支持设计用于c-Met体内评估的新型且更有效的PET探针。
